Mechanisms of actio of poly-plat, a novel platinum antineoplastic agent

Action of Cisplatin (cis-dichlorodiammine platinum II) and Poly-Plat [poly-[(trans-1,2-diaminocyclohexane) pla-tinum]-carboxyamylose] on tumor cells was examined using human fibrosarcoma (HT1080) and Walker rat carcinoma (WRC-256) in culture. These cells were treated with Poly-Plat (10 microg/ml) or Cisplatin (10 mg/ml) for 2-5 days. Peritoneal macrophages were treated with Cisplatin (10 microg/ml) or Poly-Plat (10 microg/ml) for 2 hours and allowed to grow in normal medium for 48 hours. Supernatants from treated macrophages were collected at 0, 4, 12, 24 and 48 hours and IL-2 levels were examined using ELISA technique. The cytotoxicity of these supernatants was examined using HT1080 and WRC-256 cells. Apoptotic assays were used to determine the cytotoxic effects of drugs and macrophage supernatants on tumor cells. These results demonstrate the ability of Poly-Plat to arrest the growth of tumor cells and activate macrophages to induce apoptosis in the cell lines tested.